HCV Hi hli hHCV: Highlights From EASL 2013...HCV Hi hli hHCV: Highlights From EASL 2013 Alex...

HCV Hi hli hHCV: Highlights From EASL 2013Alex Thompson MBBS PhD FRACP

From EASL 2013Alex Thompson, MBBS, PhD, FRACPSt. Vincent’s HospitalMelbourne, Australia,

Jointly sponsored by the Duke University School of Medicineand The Chronic Liver Disease Foundation

1

Disclosures

Alex Thompson has indicated he is:

• An advisory board member for Abbott Pharmaceuticals, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Janssen, M k N ti d R hMerck, Novartis, and Roche

• A speaker for Bayer Pharmaceuticals and Bristol-Myers Squibb

• A PI for Gilead, Merck, and Roche

2

HCV: Highlights From EASL 2013HCV: Highlights From EASL 2013

– IFN-containing regimens

• Current treatments

• Next step treatments

IFN f i– IFN-free regimens

3

H Fontaine1* C Hezode2 C Dorival3 D Larrey4 F Zoulim5 V De Ledinghen6 V Canva7 L Alric8H. Fontaine , C. Hezode , C. Dorival , D. Larrey , F. Zoulim , V. De Ledinghen , V. Canva , L. Alric ,M. Bourlière9, S. Pol10, T. Poynard11, G. Riachi12, P.-H. Bernard13, J.-J. Raabe14, J. Gournay15, S. Métivier16,J.-M. Pawlotsky17, D. Samuel18, Y. Barthe3, F. Carrat3, J.-P. Bronowicki19, ANRS CO 20 CUPIC Study Group

1Hepatology Unit, Cochin Hospital AP-HP, Paris, 2Hepatology Unit, Henri Mondor Hospital, Créteil, 3UMR-S 707, INSERM, Paris, 4Hepatology Unit, Saint-Eloi Hospital, Montpellier, 5U871, INSERM, Lyon, 6Hepatology

Unit, Haut Leveque Hospital, Bordeaux, 7Hepatology Unit, Claude Huriez Hospital, Lille, 8Medecine Unit, Purpan Hospital, Toulouse, 9Hepatology Unit, Saint Joseph Hospital, Marseille, 10Hepatology Unit, Cochin Hospital, 11Hepatology Unit, Pitié-Salpétrière Hospital, Paris, 12Hepatology Unit, Charles Nicolle Hospital, p p gy p p p gy p

Rouen, 13Hepatology Unit, Saint-André Hospital, Bordeaux, 14Hepatology Unit, Bon Secours Hospital, Metz, 15Hepatology Unit, Nantes Hospital, Nantes, 16Hepatology Unit, Purpan Hospital, Toulouse, 17Virology Unit,

Henri Mondor Hospital, Créteil, 18Hepatology Unit, Paul Brousse Hospital, Villejuif, 19Hepatology Unit,Brabois Hospital, Nancy, France.

4

p , y,

*[email protected]

CUPIC: French early access programCUPIC: French early access program– EASL 2012 interim report after 16 weeks of treatment

• Increased SAEs and deaths

– Design: cohort study• Selection of boceprevir or telaprevir made by the clinician

– Patients• Genotype 1• Patients with compensated cirrhosis

– Approximately 1/3 would not have qualified for phase 3 trials

• Prior relapse and partial response – Prior null response was an exclusion criteria, though a number were enrolled

– Regimens• Standard protocols for boceprevir (lead-in) and telaprevir• 48 weeks for all patients• RBV dose reduction protocol was conservative

5

H. Fontaine et al, Abstract 60. EASL, April 2013

CUPIC SVR12 Results100

CUPIC SVR12 Results

80

%)

Boceprevir

41

51

4040

53

3240

60

SVR

12 (%

Telaprevir

11

32 29

20

S

32 43 8

0All patients Prior relapse Prior partial Prior null

4385

3280

19

79190

61116

43135

828

118295

6


CUPIC: French early access programCUPIC: French early access program– Predictors of response

Predictors OR 95%Cl p-value

R l P ti lRelapsers vs Partial or null responders 2.03 1.38-3.00 0.0003

Genotype 1b vs 1 92 1 3 2 84 0 0011Genotype 1b vsGenotype non 1b 1.92 1.3-2.84 0.0011

7


CUPIC: French early access programCUPIC: French early access programBoceprevir (n=190) Telaprevir (n=295)

Serious adverse event 321 in 97 patients (51.0%) 535 in 160 patients (54.2%)

Deaths* 3 (1.6%) 7 (2.4%)

Grade 3/4 infections 8 (4.2%) 27 (9.1%)

Hepatic decompensation 9 (4.7%) 15 (5.1%)

R h (G d 3 / SCAR) 2 (1 0%) / 16 (5 4%) / 2 (0 6%)Rash (Grade 3 / SCAR) 2 (1.0%) / - 16 (5.4%) / 2 (0.6%)

Anemia (Hb < 8g/dL) 19 (10%) 38 (12.9%)

EPO use / blood TF 119 (62 6%) / 26 (13 7%) 168 (57%) / 53 (18%)

TVR* – 3 septicemia, 1 variceal bleed, 1 HE, 1 pulm neoplasia, 1 pneumoniaBOC* – 1 pulm infection, 1 aneurysmal bleed, 1 septicemia

EPO use / blood TF 119 (62.6%) / 26 (13.7%) 168 (57%) / 53 (18%)

8


CUPIC: French early access programCUPIC: French early access program

– Summary:y

• Large “real life” cohort of patients with cirrhosis

• SVR12 rate comparable to subgroup of patients with severe fibrosis or cirrhosis of phase III studies.

• Increased risk of serious adverse events, particularly severe infections and anemiainfections and anemia

9


D R Nelson1* F Poordad2 J J Feld3 M W Fried4 I M Jacobson5 P J Pockros6 M S S lko ski7D.R. Nelson1*, F. Poordad2, J.J. Feld3, M.W. Fried4, I.M. Jacobson5, P.J. Pockros6, M.S. Sulkowski7,S. Zeuzem8, L. Bengtsson9, S. George9, M.I. Friedman9, on behalf of the CONCISE Study Team

1University of Florida College of Medicine, Gainesville, FL, 2University of Texas Health Science Center, San Antonio TX USA 3Toronto Western Hospital Liver Center Toronto ON Canada 4University ofSan Antonio, TX, USA, Toronto Western Hospital Liver Center, Toronto, ON, Canada, University of North Carolina School of Medicine, Chapel Hill, NC, 5Weill Cornell Medical College, New York, NY, 6Scripps Clinic, La Jolla, CA, 7Johns Hopkins University School of Medicine, Baltimore, MD, USA, 8Johann Wolfgang Goethe University Hospital, Frankfurt/Main, Germany, 9Vertex Pharmaceuticals

I d C b id MA USAIncorporated, Cambridge, MA, USA.

*[email protected]

10

CONCISECONCISE – Patients

• IL28B CC (favorable genotype)IL28B CC (favorable genotype)• Treatment-naïve or prior relapse • No cirrhosis

T t t– Treatment• Peginterferon alfa-2a 180 mcg, SC, weekly• Ribavirin 1000/1200 mg dailyg y• Telaprevir 1125 mg bid

– RegimenP ti t ith RVR d i d 2 1 t k 12• Patients with RVR were randomized 2:1 at week 12– T12/PR12– T12/PR24

11

D.R. Nelson et al, Abstract 818. EASL, April 2013

CONCISE Interim SVR12CONCISE Interim SVR12

8797100

80

)

40

60

SVR

12 (%

)

20

40S

74 29

0T12PR12 T12PR24

85 30

12


CONCISECONCISE

– Conclusion

• High SVR rates from the CONCISE study interim analysis suggest the potential for the defined IL28B CC patients with gg p pRVR to shorten duration of telaprevir plus peginterferon/ribavirin to 12 weeks.

13


Alexander Thompson1, Steve Han2, Mitchell Shiffman3, Lorenzo Rossaro4, Reem Ghalib5, Kimberly L. Beavers6, Stephen Pianko7, Xiaoru Wu8, James Trenkle8, Bittoo Kanwar8, Mani Subramanian8, John

McHutchison8, Andrew J. Muir9, Sam Lee10, Jacob George11

1St. Vincent’s Hospital Melbourne, Australia; 2University of California, Los Angeles, CA, USA; 3Liver Institute of Virginia Norfolk VA USA; 4University of California Davis Sacramento CA USA;Liver Institute of Virginia, Norfolk, VA, USA; University of California, Davis, Sacramento, CA, USA;

5The Liver Institute at Methodist Dallas Medical Center, Dallas, TX, USA; 6Asheville Gastroenterology Associates, Asheville, PA, USA; 7Monash Medical Center, Clayton, Australia;

8Gilead Sciences, Foster City, CA, USA; 9 109Duke Clinical Research Institute, Durham, NC, USA; 10University of Calgary, Calgary, Canada;

11Westmead Hospital, Westmead NSW, Australia

14

Study DesignWeek 2 or 4 response SVR12

Week 20 6 124 24 36

LDV + GS-9451+ PEG/RBV

Arm 1n=123

PEG/RBVArm 2n=121

– Arm 1 patients who achieved HCV RNA <LLOQ at Week 2 were rerandomized to stop treatment at week 6 or 12

n=121

stop treatment at week 6 or 12 – Arm 2 patients who achieved HCV RNA <LLOQ at Week 4 received 24 weeks of

treatment– Study was modified due to case of pancytopenia*

15

Study was modified due to case of pancytopenia*3 cases of pancytopenia in combination studies of 2 DAAs + PEG/RBV. LLOQ, lower limit of quantitationA. Thompson et al, Abstract 64. EASL, April 2013

Results: Early Antiviral ResponseResults: Early Antiviral Response92* 92100

LDV + GS-9451 PEG/RBV

80

Q (%

)

+ PEG/RBV

PEG/RBV

43*40

60

nts

<LLO

Q

1820

40

Patie

n

0W k 2 W k 4

113/123 22/121 113/123 52/121

Week 2 Week 4

16

*Patients in Arms 1 and 2 whose RNA was >LLOQ at Week 2 or 4 were offered treatment as part of retreatment substudy.A. Thompson et al, Abstract 64. EASL, April 2013

Results: SVR12 in Early RespondersResults: SVR12 in Early Responders

89100 120

73

60

80

%)

79*

98**

80

100

%)

40

60

SVR

12 (% 101/113

40

60

SVR

12 (%

0

20

0

20

Arm 1: 6 + 12 weeks combined

Arm 2: PEG/RBV 6 Weeks 12 Weeks

*9 failures were relapsers; 2 were discontinuations

17

9 failures were relapsers; 2 were discontinuations.**12 week failure was a discontinuation.A. Thompson et al, Abstract 64. EASL, April 2013

ConclusionsConclusions– High SVR rates with 6 and 12 weeks of treatment

ith LDV GS 9451 PEG/RBV i t t t ïwith LDV + GS-9451 + PEG/RBV in treatment-naïve, non-cirrhotic, IL28B CC patients• 6 weeks is the shortest duration of treatment that has ever

been explored

Alth h thi i ill t f d th t d– Although this regimen will not go forwards, the study provides proof-of-concept that very short duration t t t i ibl f CC IL28B ti ttreatment is possible for CC IL28B patients• IFN-sparing

C t i

18

• Cost-sparingA. Thompson et al, Abstract 64. EASL, April 2013

I. Jacobson1*, G.J. Dore2, G.R. Foster3, M.W. Fried4, M. Radu5, V.V. Rafalskiy6, L. Moroz7, A. Craxì8, M. Peeters9, O. Lenz9, S. Ouwerkerk-Mahadevan10, R. Kalmeijer11, M. Beumont-Mauviel9

1Weill Cornell Medical College, New York, NY, USA, 2Kirby Institute, University of New South Wales, Sydney, NSW, Australia, 3Queen Mary University of London, Barts Health, London, UK, 4University of

North Carolina at Chapel Hill, Chapel Hill, NC, USA, 5Institutul de Boli infectioase, Bucharest,North Carolina at Chapel Hill, Chapel Hill, NC, USA, Institutul de Boli infectioase, Bucharest, Romania, 6Smolensk Regional Clinical Hospital, Smolensk Oblast, Russia, 7Vinnytsia National

Medical University, Vinnytsia, Ukraine, 8Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone, Palermo, Italy, 9Janssen Infectious Diseases BVBA, 10Janssen Research & Development,

B B l i 11J Gl b l S i LLC Tit ill NJ USABeerse, Belgium, 11Janssen Global Services, LLC, Titusville, NJ, USA.

*[email protected]

19

QUEST-1QUEST-1– Simeprevir: potent, once-daily, oral HCV NS3/4A protease inhibitor– Phase III, randomized, double-blind, placebo-controlled trialPhase III, randomized, double blind, placebo controlled trial – Patients

• Treatment naïve genotype 1 infection– Regimen

• PEG + RBV + simeprevir 150 mg qd• PEG + RBV + placebop

– Algorithm• Simeprevir for first 12 weeks• Response guided therapy• Response guided therapy

– RVR: PEG/RBV x 24 weeks – No RVR: PEG/RBV x 48 weeks

20

I. Jacobson et al, Abstract 1425. EASL, April 2013

QUEST 1: SVR12 rates100

QUEST-1: SVR12 ratesP<0.0001

8080

)

50

40

60

SVR

12 (%

20

S

210 65

0PEG+RBV+SIMEPREVIR PEG+RBV+PLACEBO

210264

65130

21

* 85% achieved RVR and qualified for short duration therapyI. Jacobson et al, Abstract 1425. EASL, April 2013

QUEST 1: SVR12 rates in subgroups

120

QUEST-1: SVR12 rates in subgroupsSIM + PR PR

8390 94

767880

100

70 7176

6560

49 5242

60

80

28 2420

40

152/ 54/ 54/ 11/ 105/ 36/ 105/ 29/ 72/ 29/ 114/ 32/ 24/ 4/

0F0-F2 F3-F4 1a 1b/other CC CT TT

Fibrosis Genotype IL28B genotype

152/183

54/90

54/77

11/40

105/147

36/74

105/117

29/56

72/77

29/37

114/150

32/76

24/37

4/17

22


Fibrosis Genotype IL28B genotype

QUEST-1 conclusionsQUEST-1 conclusions– Simeprevir 150 mg + PEG/RBV was highly effective

i t HCV t 1 t t t ï ti t ithagainst HCV genotype 1 treatment naïve patients with SVR12 80%.

– Most patients (85%) receiving simeprevir were able to shorten therapy to 24 weeks.

– Simeprevir 150 mg + PEG/RBV was generally well tolerated• Rates of anemia and rash were similar in the simeprevir and

placebo groups

23


E. Lawitz1*, D. Wyles2, M. Davis3, M. Rodriguez-Torres4, K.R. Reddy5, K.V. Kowdley6,E. Svarovskaia7, D. Jiang7, J. McNally7, D.M. Brainard7, W.T. Symonds7, J.G. McHutchison7,

L. Nyberg8, Z. Younossi9

1Alamo Medical Research, San Antonio, TX, 2University of California, San Diego, San Diego, CA, 3DigestiveCARE-South Florida Center of Gastroenterology, Wellington, FL, USA, 4Fundación de

Investigación, San Juan, Puerto Rico, 5University of Pennsylvania School of Medicine, Philadelphia, PA, 6Digestive Diseases Unit, Virginia Mason Medical Center, Seattle, WA, 7Gilead Sciences, Inc., Foster City, 8Kaiser Permanente, San Diego, CA, 9Inova Fairfax Hospital, Falls Church, VA, USA.

*l i @ li*[email protected]

24

Week 0 12 24Open labelWeek 0 12 24 Open label

SOF + Peg-IFN + RBV, n=327 SVR12

DemographicsMean age, y (range) 52 (19-70)

Male, n (%) 209 (64)

Black, n (%) 54 (17)

Hispanic, n (%) 46 (14)p , ( ) ( )

Mean BMI, kg/m2 (range) 29 (18-56)

IL28B CC, n (%) 95 (29)

GT 1 n (%) 292 (89)GT 1, n (%) 292 (89)

GT 4/5/6, n (%) 35 (11)

Mean baseline HCV RNA, log10 IU/mL (range) 6.4 (2.1-7.6)

Ci h i (%) 54 (17)

25

Cirrhosis, n (%) 54 (17)E. Lawitz et al, Abstract 1411. EASL, April 2013

NEUTRINO: SVR12 by Genotype SVR12 in cirrhotics and

100

y yp

9280

100

%) 90 89

96 100noncirrhotics

80

80

80

A <L

LOQ

(%

s

40

60

40

60

h H

CV

RN

A

% P

atie

nts

20252/273

43/54

20

atie

nts

with

295/327

261/292

27/28 7/7

0noncirrhotic cirrhotic

273 540

Overall GT 1 GT 4 GT 5,6

Pa

327 292 28 7/7

SVR12

26

E. Lawitz et al, Abstract 1411. EASL, April 2013

ConclusionsConclusions– 12 weeks of treatment with SOF + PEG-IFN + RBV

hi d 90% SVR12 i t t t ï ti tachieved 90% SVR12 in treatment naïve patients with HCV genotype 1,4,5,or 6

– No virological breakthrough was observed - relapse accounted for all virologic failures

– This regimen was well tolerated• Only 7 patients discontinued treatment (2%)• Similar rate to FISSION (SOF + RBV in TN genotype

2/3 patients)

27

E. Lawitz et al, Abstract 1411. EASL, April 2013

HCV: Highlights From EASL 2013HCV: Highlights From EASL 2013

– IFN-containing regimens

• Current treatments

N t t t t t• Next step treatments

– IFN-free regimensg

28

E. Gane1*, E. Lawitz2, M. Rodriguez-Torres3, S. Gordon4, H. Dvory-Sobol5, S. Arterburn5, J. McNally5 D M Brainard5 W T Symonds5 J G McHutchison5 A Sheikh6 A Mangia7McNally , D.M. Brainard , W.T. Symonds , J.G. McHutchison , A. Sheikh , A. Mangia

D.R. Nelson1*, J. Feld2, K.V. Kowdley3, M.T. Al-Assi4, M. Lin5, H. Mo5, J. McNally5, D.M. Brainard5, W T S d 5 J G M H t hi 5 K P t l6 S C G d 71W.T. Symonds5, J.G. McHutchison5, K. Patel6, S.C. Gordon71

I. Jacobson1*, E.M. Yoshida2, M. Sulkowski3, D.R. Nelson4, E. Svarovskaia5, D. An5, J. McNally5, D M Brainard5 W T Symonds5 J G McHutchison5 S Pianko6 K V

29

D.M. Brainard5, W.T. Symonds5, J.G. McHutchison5, S. Pianko6, K.V.

Week 0 12 24 36

SOF + RBV, n=256 SVR12

Peg-IFN + RBV (SOC), n=243 SVR12RBV dose 1000-1200 mg/day for SOF + RBV and 800 mg/day for Peg-IFN + RBV.

Week 0 12 16 24 28

SOF + RBV, n=103 Placebo SVR12


SOF dose 400 mg once daily; RBV dose 1000-1200 mg/day.


Week 0 12 24

30

Placebo, n=71 SVR12SOF dose 400 mg once daily; RBV dose 1000-1200 mg/day.

6080

100

SOF RBV 12 W k2 (%

) 67 67

9778

56 63

0204060

Overall GT 2 GT 3

SOF + RBV 12 Weeks

Peg-IFN + RBV 24 WeeksSVR

12

170/253

162/243

68/70

52/67

102/183

110/176

80100

P <0.001

%)

50 7386 94

62

P <0.001

020406080

SOF + RBV 12 weeks

SOF + RBV 16 weeksSVR

12 (%

50/100

69/95

31/36

30/32 19/64

39/63

5030

62

Overall GT 2 GT 3

10093

20406080

100

SVR

12 (%

)

161/207 101/109 60/98

7861

SOF + RBV 12 weeks

31

0Overall GT 2 GT 3

S 161/207 101/109 60/98

6080

100

SOF RBV 12 W k2 (%

)

98 82 91

6234 30

61 71

02040

No cirrhosis Cirrhosis No cirrhosis Cirrhosis

SOF + RBV 12 Weeks

Peg-IFN + RBV 24 WeeksSVR

12

30

58/59

44/54

10/11 8/1

3

89/145

99/139 13/38 11/37

80100

(%)

96 100

6078

GT 2 GT 3

80100

3763

61

0204060

N Ci h i Ci h i

SVR

12

25/26

23/23 6/10 7/9

0204060

N Ci h i Ci h i

SOF + RBV 12 weeks

SOF + RBV 16 weeks

14/38

3719

25/40 5/26

14/23

No Cirrhosis Cirrhosis

10092 94

GT 2No Cirrhosis Cirrhosis

GT 3

20406080

100

No cirrhosis

Cirrhosis

SVR

12 (%

)

85/92 67/84

68

21

16/17 3/14

32

0GT 2 GT 3

S 85/92 67/8416/17 3/14

Conclusions: SOF + RBV for Genotype 2/3Conclusions: SOF + RBV for Genotype 2/3– SOF + RBV leads to excellent results (SVR12 > 90%) in genotype 2 TN

patients with and without cirrhosis– SVR rates were lower in genotype 2 TE patients with cirrhosis compared

to non-cirrhosisSOF + RBV led to similar results as PEG + RBV for genotype 3 TN– SOF + RBV led to similar results as PEG + RBV for genotype 3 TN patients

• Lowest rates observed in patients with cirrhosis

– SOF + RBV for 12 weeks is suboptimal for genotype 3 TE patients• 16 weeks total duration significantly increased SVR rates

– SOF + RBV well tolerated with fewer adverse events than PEG + RBVSOF RBV well tolerated with fewer adverse events than PEG RBV– No virological breakthrough was observed, no resistance in relapsers– Genotype 3 ≠ genotype 2 HCV

33

• Strategies to improve genotype 3 results are needed

K V Kowdley1* E Lawitz2 F Poordad2 D E Cohen3 D Nelson4 S Zeuzem5 G T Everson6K.V. Kowdley1 , E. Lawitz2, F. Poordad2, D.E. Cohen3, D. Nelson4, S. Zeuzem5, G.T. Everson6,P. Kwo7, G.R. Foster8, M. Sulkowski9, W. Xie3, L. Larsen3, A. Khatri3, T. Podsadecki3, B. Bernstein31

Digestive Disease Institute, Virginia Mason Medical Center, Seattle, WA, 2University of Texas Health Science Center San Antonio TX 3Abbott Laboratories Abbott Park IL 4University of Florida CollegeScience Center, San Antonio, TX, Abbott Laboratories, Abbott Park, IL, University of Florida College

of Medicine, Gainesville, FL, USA, 5J.W. Goethe University, Frankfurt, Germany, 6University of Colorado Denver, Aurora, CO, 7Indiana University, Indianapolis, IN, USA, 8Queen Mary’s University of

London, Barts Health, London, UK, 9Johns Hopkins University, Baltimore, MD, USA.

*[email protected]

34

AVIATORAVIATOR– Phase 2, randomized, open-label, multicenter study– PatientsPatients

• Genotype 1 (66% genotype 1a)• Treatment-naïve and prior null response• Non-cirrhotic

– Medications• ABT 450/r (HCV protease inhibitor boosted with ritonavir 100 mg)• ABT-450/r (HCV protease inhibitor boosted with ritonavir 100 mg)• ABT-267 (NS5A inhibitor) • ABT-333 (non-nucleoside NS5B inhibitor)• Ribavirin

– Duration8 12 d 24 k

35

K.V. Kowdley et al, Abstract 3. EASL, April 2013

• 8, 12 and 24 weeks

SVR12 SVR24 VBT/N SVR12 SVR24** VBT/SVR12 (%)

SVR24(%)

VBT/Relapse

89 88 0/10

85 83 1/4

N Regimen/duration SVR12 (%)

SVR24(%)

VBT/Relapse

80 ABT450 ABT267 ABT333 RBV 89 88 0/10

41 ABT450 ABT333 RBV 85 83 1/4naiv

e

91 89 1/8

90 87 1/5

99 96 0/1

79 ABT450 ABT267 RBV 91 89 1/8

79 ABT450 ABT267 ABT333 90 87 1/5

79 ABT450 ABT267 ABT333 RBV 99 96 0/1Trea

tmen

t n

99 96 0/1

93 90 0/2

79 ABT450 ABT267 ABT333 RBV 99 96 0/1

80 ABT450 ABT267 ABT333 RBV 93 90 0/2

Week 8 12 24

T

SVR12 (%)

SVR24(%)

VBT/Relapse

89 89 0/5

93 93 3/0

N Regimen/duration SVR12 (%)

SVR24(%)

VBT/Relapse

45 ABT450 ABT267 RBV 89 89 0/5

45 ABT450 ABT267 ABT333 RBV 93 93 3/0resp

onse

93 93 3/0

98 95 1/0

45 ABT450 ABT267 ABT333 RBV 93 93 3/0

43 ABT450 ABT267 ABT333 RBV 98 95 1/0Nul

l

** 8 patients who achieved SVR12 did not return > 24 weeks and were counted as virological failures for SVR24

36

8 patients who achieved SVR12 did not return > 24 weeks and were counted as virological failures for SVR243 patients relapsed between SVR12 and SVR24K.V. Kowdley et al, Abstract 3. EASL, April 2013

AVIATOR conclusionsAVIATOR conclusions

– Comparable SVR12 and 24 seen with 12 and 24 weeks of treatment

• Selection of a 12-week duration of therapy in these populationsSelection of a 12-week duration of therapy in these populations

– SVR rates >90% were achieved in naïve and prior null responder patients with a 3-DAA+RBV regimen

• No clinically meaningful differences were observed by sex, y g y ,HCV subtype, IL28B genotype, baseline HCV-RNA or severity of fibrosis.

37

K.V. Kowdley et al, Abstract 3. EASL, April 2013

1 2 3 4 5 6M.S. Sulkowski1*, D.F. Gardiner2, M. Rodriguez-Torres3, K.R. Reddy4, T. Hassanein5, I. Jacobson6,E. Lawitz7, A.S. Lok8, F. Hinestrosa9, P.J. Thuluvath10, H. Schwartz11, D.R. Nelson12, G.T. Everson13,

T. Eley2, M. Wind-Rotolo14, S.-P. Huang14, M. Gao15, F. McPhee15, D. Hernandez15, D. Sherman2,R. Hindes16, W. Symonds17, C. Pasquinelli2, D.M. Grasela2, AI444040 Study Group

1Johns Hopkins University, Baltimore, MD, 2Bristol-Myers Squibb, Hopewell, NJ, USA, 3Fundación de Investigación, San Juan, Puerto Rico, 4University of Pennsylvania, Philadelphia, PA, 5Southern California

Liver Center, Coronado, CA, 6Weill Cornell Medical College, New York, NY, 7Texas Liver Institute, University of Texas Health Science Center San Antonio TX 8University of Michigan Ann Arbor MI 9Orlando ImmunologyTexas Health Science Center, San Antonio, TX, 8University of Michigan, Ann Arbor, MI, 9Orlando Immunology

Center, Orlando, FL, 10Mercy Medical Center, Baltimore, MD, 11Miami Research Associates, South Miami, 12University of Florida, Gainesville, FL, 13University of Colorado, Denver, CO, 14Bristol-Myers Squibb,

Princeton, NJ, 15Bristol-Myers Squibb, Wallingford, CT, 16Consultant, 17Gilead Sciences, Foster City, CA, USA.

38

*[email protected]

BackgroundBackground – Patients who experience virologic failure on telaprevir or

boceprevir-based regimens currently have no treatment options

– Daclatasvir (DCV): NS5A inhibitor

– Sofosbuvir (SOF): nucleotide NS5B polymerase inhibitor

– DCV plus SOF with or without RBV achieved SVR4 in 98% of 126 HCV GT 1-infected treatment-naive patients (Sulkowski et al AASLD 2012)(Sulkowski et al. AASLD 2012)

Aim: T l t th ffi d f t f DCV l SOF ith ith t– To evaluate the efficacy and safety of DCV plus SOF with or without RBV for 24 weeks in HCV GT 1-infected patients who failed prior treatment with TVR or BOC + pegIFN-alfa/RBV

39

M.S. Sulkowski et al, Abstract 1417. EASL, April 2013

Study Design

Prior TVR/BOCn = 21 DCV 60 mg QD + SOF 400 mg QD Follow-up

Study Design

Prior TVR/BOC failures, GT 1a/1b(N = 41) Follow-upn = 20 DCV 60 mg QD + SOF 400 mg QD + RBV

Week 24SVR4

SVR12• Patients• Genotype 1, non-cirrhotic• Prior nonresponse, relapse, or breakthrough during treatment

i h PEG/RBV TVR BOCwith PEG/RBV + TVR or BOC• Patients who discontinued TVR or BOC due to an adverse

event were excluded

40


event were excluded

Virologic response100

tient

s)

Virologic responseDCV + SOF

60

80

OQ

(%

pat

DCV + SOF + RBV

Missing

20

40

RN

A <

LLO Missing

0

EOT

HC

V

Week 2 SVR4

N =

Week 4

21 20

SVR12

21 20 21 20 21 20 21 20

4 12

– 1 patient missing at post-treatment (PT) Week 12: HCV RNA was undetectable at PT Week 4 and at PT Week 2421/41 patients have reached PT Week 24; all have achieved SVR

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– 21/41 patients have reached PT Week 24; all have achieved SVR24

ConclusionConclusion

– The all-oral, once-daily combination of DCV + SOF with or without RBV achieved SVR in all HCV GT 1-infected patients (n=41) who failed prior treatment with TVR or BOC + pegIFN-alfa/RBV

DCV + SOF with or without RBV was well tolerated– DCV + SOF with or without RBV was well tolerated

• No grade 3 or 4 hepatic or hematologic abnormalities

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HCV Hi hli hHCV: Highlights From EASL 2013...HCV Hi hli hHCV: Highlights From EASL 2013 Alex...

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